There are many compounds that contain amide groups which have desirable pharmacological activity. For example, oxazolidinone derivatives containing an amide group are known to exhibit a variety of biological activities.
Oxazolidinone derivatives have been shown to be inhibitors of monoamine oxidase-B, an enzyme implicated in Parkinson's disease. Ding et al., J. Med. Chem. 36:3606-3610 (1993).
Scientists have reported that certain oxazolidinone derivatives exhibit beneficial antibacterial effects. For instance, N-[3-[3-fluoro-4-(morpholin-4-yl)phenyl]2-oxooxazolidin-5(s)-ylmethyl] acetamide (below) has been reported to be useful for the treatment of bacterial infections. Lizondo et al., Drugs of the Future, 21:1116-1123 (1996). 
A ten step synthesis of oxazolidinone antibiotics has been described in U.S. Pat. No. 5,547,950. A four step synthesis of the antibacterial compound U-100592 also has been reported. Schauss et al., Tetrahedron Letters, 37:7937-7940 (1996). A five step preparation of enantiomerically pure cis- and trans-N-(propionyl)hexahydrobenzoxazolidin-2-ones further was reported in De Parrodi et al., Tetrahedron: Asymmetry, 8:1075-1082 (1997).
The synthesis of the oxazolidinone antibacterial agent shown below has been reported. Wang et al., Tetrahedron, 45:1323-1326 (1989). This oxazolidinone was made using a process that included the reaction of an aniline with glycidol to provide an amino alcohol, and the diethylcarbonate mediated cyclization of the amino alcohol to afford an oxazolidinone. 
The synthesis of oxazolidinone antibacterial agents, including the compound shown below has been reported. U.S. Pat. No. 4,705,799. The process used to make the compound shown below included a metal mediated reduction of a sulfonyl chloride to provide a sulfide. 
The synthesis of oxazolidinone antibacterial agents, including the pyridyl compound shown below has been reported. U.S. Pat. No. 4,948,801. The process used included an organometallic mediated coupling of an organotin compound and an aryl iodide. 
U.S. Pat. No. 5,652,238 discloses carboxylic and phosphate esters of substituted-hydroxyacetyl piperazine phenyl oxazolidinones.
U.S. Pat. No. 5,688,792 discloses substituted oxazine and thiazine oxazolidinone useful as antibacticals.
PCT International Publication WO 98/54161 discloses oxazolidinone antibacterial agents having a thiocarbonyl functionality.
U.S. Pat. No. 5,968,962 and PCT International Publication WO 99/29688 discloses phenyloxazolidinones having a C—C bond to 4-8 membered heterocyclic rings.
U.S. Pat. No. 5,952,324 discloses bicyclic oxazine and thiazine oxazolidinone useful as antibacticals.
PCT publications, WO 99/64416, WO 99/64417, and WO 00/21960 disclose oxazolidinone derivatives useful as antibacterial agents.
PCT Publication, WO 00/10566 discloses isoxazolinones useful as antibacterial agents.
U.S. Pat. No. 5,880,118 discloses substituted oxazine and thiazine oxazolidinone antimocrobials.
U.S. Pat. No. 6,968,962 discloses phenyloxazolidinones having a C—C bond to 4-8 membered heterocyclic rings.
U.S. Pat. No. 5,981,528 discloses antibiotic oxazolidinone derivatives.
U.S. patent application Ser. No. 60/236,595 discloses N-({(5S)-3-[4-(1,1-dioxido-4-thiomorpholinyl)-3,5-difluorophenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide.
PCT publications, WO 99/64416, WO 99/64417, and WO 00/21960 disclose isoxazolinone derivatives useful as antibacterial agents.
PCT publication, WO 00/10566 discloses isoxazolinones useful as antibacterial agents.
U.S. Pat. No. 5,164,510 discloses 5′-indolinyloxazolidin-2-ones of formula XI which are useful as antibacterial agents.
U.S. Pat. Nos. 5,036,092; 5,036,093; 5,039,690; 5,032,605 and 4,965,268 disclose aminomethyl oxazolidinyl aza cycloalkylbenzene derivatives useful as antibacterial agents.
U.S. Pat. Nos. 5,792,765 and 5,684,023 disclose substituted isoxazolinones useful as antibacterial agents.
International Publication No. WO 97/09328 discloses phenyloxazolidinones having a C—C bond to 4-8 membered heterocyclic rings useful as antimicrobial agents.
PCT International Publication WO 93/23384 discloses oxazolidinones containing a substituted diazine moiety and their use as antimicrobials.
PCT International Publication WO 95/07271 discloses substituted oxazine and thiazine oxazolidinones and their use as antimicrobials.
However, even though some amide-containing compounds have been shown to be extremely effective in the treatment of certain physiological disorders, some of these compounds have a low bioavailability due to their low water solubility and/or low permeability through biological barriers, such as the blood brain barrier and the intestinal barrier.
In order to increase the bioavailability of certain amines, peptides and peptidomimetics, prodrugs of these compounds, have been proposed. Zheng et al, Tetrahedron Letters, 55:4237-4254 (1999), Wang et al, Journal of Controlled Release, 65:245-251 (2000) and Wang et al, Bioorganic & Medicinal Chemistry, 6:417-426 (1998). These prodrugs derivatize certain polar functional groups transiently and bioreversably to mask undesirable physical chemical characteristics of the groups without permanently altering the pharmacological properties of the molecules and have been used very successfully in cases where the prodrug derivatization involves converting a carboxyl or a hydroxyl functional group into an ester which can be readily hydrolyzed in vivo either chemically or enzymatically. However, this strategy has not been successfully used in the case of an amide group due to the chemical stability thereof.
As such, there is a need for amide-containing compounds having an improved water-solubility and bioavailability and for methods for synthesizing these compounds.